تفاعل #495790

معادلة التفاعل

CDI

3-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-propionic acid

MgCl2

ethyl potassium malonate

→

5-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe reaction was stirred for 15 h at 20° C
2. 2
   تركيزThe crude was concentrated under reduced pressure
3. 3
   أخرىthen partitioned between water and EtOAc
4. 4
   أخرىThe layers were separated
5. 5
   تجفيفthe organic layer was dried over MgSO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated under reduced pressure
8. 8
   أخرىThe crude was purified by chromatography on silica gel (
9. 9
   غسيلelution with Hept/EtOAc/DCM/MeOH

الإجراء التجريبي

To a solution of CDI (4 eq) in THF was added 3-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-propionic acid, compound 65 (1 eq.), the mixture was stirred for 4 h at 20° C., then MgCl2 (4 eq.) and ethyl potassium malonate (5 eq.) were added. The reaction was stirred for 15 h at 20° C. The crude was concentrated under reduced pressure then partitioned between water and EtOAc. The layers were separated and the organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with Hept/EtOAc/DCM/MeOH: 50/50/95/5 then 50/50/90/10) to afford 5-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester.

المصدر